EP0909171B1 - Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1 - Google Patents

Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1 Download PDF

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Publication number
EP0909171B1
EP0909171B1 EP97922035A EP97922035A EP0909171B1 EP 0909171 B1 EP0909171 B1 EP 0909171B1 EP 97922035 A EP97922035 A EP 97922035A EP 97922035 A EP97922035 A EP 97922035A EP 0909171 B1 EP0909171 B1 EP 0909171B1
Authority
EP
European Patent Office
Prior art keywords
igf
acetylcarnitine
isovalerylcarnitine
propionylcarnitine
pct
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Revoked
Application number
EP97922035A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0909171A1 (en
Inventor
Claudio De Simone
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mendes SRL
Sigma Tau Industrie Farmaceutiche Riunite SpA
Original Assignee
Mendes SRL
Sigma Tau Industrie Farmaceutiche Riunite SpA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=11404324&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0909171(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Mendes SRL, Sigma Tau Industrie Farmaceutiche Riunite SpA filed Critical Mendes SRL
Publication of EP0909171A1 publication Critical patent/EP0909171A1/en
Application granted granted Critical
Publication of EP0909171B1 publication Critical patent/EP0909171B1/en
Anticipated expiration legal-status Critical
Revoked legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH

Definitions

  • the present invention relates to a novel therapeutic use of L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine or pharmacologically acceptable salts thereof for increasing the levels of IGF-1 (insulin-like growth factor 1) for the therapeutic treatment or prophylaxis of cytological disorders or diseases related to IGF-1. More particularly, the present invention relates to the use of L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine or pharmacologically acceptable salts thereof for the therapeutic treatment or prophylaxis of individuals in whom IGF-1 contributes towards the pathogenesis of a particular disease or provokes cytological disorders.
  • IGF-1 insulin-like growth factor 1
  • IGF-1 promotes cell growth and differentiation.
  • the administration of IGF-1 obtained as a protein purified by molecular biology methods has made it possible to confirm the effects observed in vitro with cells, on animal models and in man.
  • the action of IGF-1 is similar to that of insulin, that is to say an increase in the uptake of glucose, a reduction in ketones and fatty acids in the serum and an increase in protein synthesis.
  • clinical studies have been undertaken in order to evaluate the efficacy of IGF-1 in a range of diseases.
  • IGF-1 has been administered to patients with type-II diabetes, to cachectic patients, to patients with ischemic damage at the neuronal, myocardial or renal level, and has been proposed for repairing and regenerating tissues (W.L. Lowe, Insulin-like growth factors, Scientific American Science and Medicine p. 62, March 1996).
  • IGF-1 may be therapeutically useful in various morbid conditions.
  • diseases or disorders which may be prevented, cured or improved by the administration of IGF-1 include neuropathies of the optic nerve and of the olfactory nerve, neuralgia of the trigeminal nerve, Bell's paralysis, arthropathy, arthritis, cervical spondylosis and hernia of the intervertebral discs, clinical syndromes of reduced height, cachexia, acute or chronic hepatic necrosis, Turner's syndrome, sarcopoenia, growth hormone insensitivity syndromes, obesity, myasthenia and heart asthenia IGF-1 moreover appears to be useful for the cicatrization of wounds, the healing of ulcers, the treatment of burns, tissue regeneration in general and in particular that of cutaneous, intestinal and hepatic tissue, and the formation of dentine.
  • the administration of L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine or pharmacologically acceptable salts thereof is capable of inducing the production of IGF-1 without the undesirable effects produced by the administration of exogenous IGF-1.
  • pharmacologically acceptable salt of L-acetylcarnitine, of L-isovalerylcarnitine or of L-propionylcarnitine is understood to refer to any salt of the above with an acid which does not give rise to undesirable toxicity or side-effects.
  • acids are well known to pharmacologists and to experts in the pharmaceutical field.
  • Non-limiting examples of such salts are: chloride; bromide; iodide; aspartate, in particular hydrogen aspartate; citrate, in particular hydrogen citrate; tartrate; phosphate, in particular hydrogen phosphate; fumarate, in particular hydrogen fumarate; glycerophosphate, glucose phosphate; lactate; maleate, in particular hydrogen maleate; orotate; oxalate, in particular hydrogen oxalate; sulphate, in particular hydrogen sulphate; trichloroacetate, trifluoroacetate and methanesulphonate.
  • the present invention relates to the use of acetyl L- carnitine only.
  • L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine or pharmaceutically acceptable salts thereof are capable of increasing the levels of IGF-1 in human biological fluids. It should be emphasized that, on the basis of extensive supporting scientific literature, the mechanism of action of L-acetylcarnitine has been focused at the metabolic level, more specifically demonstrating a protective action with respect to the mitochondria, whereas the present invention demonstrates an action mediated by the production of IGF-1.
  • the L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine or pharmaceutically acceptable salts thereof are administered in combination with vasodilatory, vascular, endocrinological, immunological, cytostatic, immunomodulatory, anti-inflammatory or cortisone pharmaceutical products, IGF-1, IGF-1 binding proteins, growth hormones and other cell growth factors such as, for example, epidermal growth factor, and erythropoietin.

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  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Biomedical Technology (AREA)
  • Obesity (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
EP97922035A 1996-07-05 1997-05-15 Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1 Revoked EP0909171B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ITRM960479 1996-07-05
IT96RM000479A IT1290801B1 (it) 1996-07-05 1996-07-05 Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili
PCT/IT1997/000113 WO1998001128A1 (en) 1996-07-05 1997-05-15 Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1

Publications (2)

Publication Number Publication Date
EP0909171A1 EP0909171A1 (en) 1999-04-21
EP0909171B1 true EP0909171B1 (en) 2004-08-18

Family

ID=11404324

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97922035A Revoked EP0909171B1 (en) 1996-07-05 1997-05-15 Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1

Country Status (11)

Country Link
US (2) US6037373A (pt)
EP (1) EP0909171B1 (pt)
JP (1) JP2000514437A (pt)
KR (1) KR100479669B1 (pt)
AT (1) ATE273701T1 (pt)
CA (1) CA2260145C (pt)
DE (1) DE69730330T2 (pt)
ES (1) ES2225968T3 (pt)
IT (1) IT1290801B1 (pt)
PT (1) PT909171E (pt)
WO (1) WO1998001128A1 (pt)

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IT1290801B1 (it) * 1996-07-05 1998-12-11 Mendes Srl Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili
US6380252B1 (en) * 1996-07-05 2002-04-30 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Use of L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine for increasing the levels of IGF-1
DE19718826A1 (de) * 1997-05-05 1998-11-12 Marion S Dr Eckmiller Verwendung biologisch aktiver Wirkstoffe zum Beeinflussen des Extrazellulär-Raumes von Sinneszellen und Verfahren zur Wirkstoff-Administrationssteuerung
IT1306178B1 (it) 1999-07-27 2001-05-30 Sigma Tau Ind Farmaceuti Uso della l-carnitina e dei suoi alcanoil derivati per la preparazionedi un medicamento utile nel trattamento del paziente affetto da
IT1316990B1 (it) * 2000-02-17 2003-05-26 Sigma Tau Ind Farmaceuti Metodo per aumentare l'espressione genica per geni trasfettati.
US20010025027A1 (en) * 2000-03-07 2001-09-27 Sonis Stephen T. Inhibition of ceramide for the prevention and treatment of oral mucositis induced by antineoplastic drugs or radiation
IT1317937B1 (it) * 2000-11-17 2003-07-15 Sigma Tau Healthscience Spa Composizione per stimolare le difese immunitarie ed il metabolismo delferro comprendente una alcanoil l-carnitina e lattoferrina.
IT1317938B1 (it) * 2000-11-17 2003-07-15 Sigma Tau Healthscience Spa Composizione per la prevenzione e/o il trattamento di alterazioni delmetabolismo lipidico, delle forme allergiche e per attivare le difese
IT1317079B1 (it) 2000-12-21 2003-05-26 Sigma Tau Ind Farmaceuti Uso della isovaleril l-carnitina per la preparazione di un medicamentoper la prevenzione e cura dell'osteoporosi.
ITRM20010708A1 (it) 2001-12-04 2003-06-04 Sigma Tau Ind Farmaceuti Uso di una alcanoil l-carnitina per il trattamento della disfunzione erettile.
US6652891B2 (en) 2001-12-12 2003-11-25 Herbasway Laboratories, Llc Co-enzyme Q10 dietary supplement
CA2369810C (en) * 2002-01-30 2007-08-07 1474791 Ontario Limited Method of treating pain
US20050106183A1 (en) * 2002-01-31 2005-05-19 Lamb Gregory B. Method of treating pain
US7700074B2 (en) * 2002-02-07 2010-04-20 Pettegrew Jay W Method and system for diagnosis of neuropsychiatric disorders including chronic alcoholism
US7407778B2 (en) 2002-02-07 2008-08-05 Pettegrew Jay W Compounds, compositions and methods for treating neuropsychiatric disorders
US7026312B2 (en) 2002-03-14 2006-04-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Substituted piperidines, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
ITRM20020492A1 (it) * 2002-10-01 2004-04-02 Sigma Tau Ind Farmaceuti Uso della propionil l-carnitina per la preparazione di un medicamento per il trattamento del glaucoma.
ITRM20020620A1 (it) 2002-12-13 2004-06-14 Sigma Tau Ind Farmaceuti Uso delle carnitine per la prevenzione e/o il trattamento dei disturbi causati dall'andropausa.
US7776913B2 (en) * 2002-12-13 2010-08-17 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Carnitines for treating or preventing disorders caused by andropause
CN1795198B (zh) * 2003-05-29 2011-08-17 杰伊·W·佩特格尤 对神经精神疾病进行医学成像所用的甘油磷酸胆碱及其衍生物
US20060257842A1 (en) * 2003-05-29 2006-11-16 Pettegrew Jay W Cryopreservation media and molecules
US8173618B2 (en) * 2003-07-25 2012-05-08 University Of Massachusetts Formulations for reducing neuronal degeneration
US20050232911A1 (en) * 2004-04-19 2005-10-20 Schreiber Brian D Prevention and treatment of metabolic abnormalities associated with excess intramyocellular lipid
EP1871883A1 (en) 2005-03-02 2008-01-02 Metanomics GmbH Process for the production of fine chemicals
JP2006347935A (ja) * 2005-06-15 2006-12-28 Masanori Ogata 炎症性サイトカインの産生が関与する疾患の予防及び／又は治療のための医薬
US20070087975A1 (en) * 2005-10-17 2007-04-19 Sigma-Tau Industrie Farmaceutiche Riunite Spa Compound useful for the prevention and treatment of left ventricular hypertrophy in dialysed patients
KR100738959B1 (ko) 2006-02-09 2007-07-12 주식회사 하이닉스반도체 반도체 메모리 장치의 센스 앰프 전원 공급 회로 및 방법
US7957213B2 (en) * 2006-02-09 2011-06-07 Hynix Semiconductor, Inc. Semiconductor memory apparatus
WO2008036682A2 (en) 2006-09-18 2008-03-27 Raptor Pharmaceutical Inc. Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates
JP5982091B2 (ja) * 2007-03-21 2016-08-31 シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニＳｉｇｍａ−Ｔａｕ Ｉｎｄｕｓｔｒｉｅ Ｆａｒｍａｃｅｕｔｉｃｈｅ Ｒｉｕｎｉｔｅ Ｓｏｃｉｅｔａ Ｐｅｒ Ａｚｉｏｎｉ インスリン耐性を有する前糖尿病患者における２型糖尿病およびその合併症の予防に有用な組成物
WO2008134828A2 (en) 2007-05-04 2008-11-13 Katholieke Universiteit Leuven Tissue degeneration protection
KR20100017460A (ko) * 2007-05-24 2010-02-16 시그마타우 인두스트리에 파르마슈티케 리우니테 에스.피.에이. 피피에이알 감마 작용물질로 인한 부작용의 예방에 유용한 조성물
US8597640B2 (en) * 2007-10-31 2013-12-03 University Of Massachusetts Lowell Over-the-counter vitamin/nutriceutical formulation that provides neuroprotection and maintains or improves cognitive performance in alzheimer's disease and normal aging
US20120077778A1 (en) 2010-09-29 2012-03-29 Andrea Bourdelais Ladder-Frame Polyether Conjugates

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US5240961A (en) * 1992-07-02 1993-08-31 Shug Austin L Method of treating reduced insulin-like growth factor and bone loss associated with aging
WO1995000137A1 (de) * 1993-06-21 1995-01-05 Bernardini, Attilio Verwendung von acylcarnitin zur behandlund von aids-krankheiten
IT1290801B1 (it) * 1996-07-05 1998-12-11 Mendes Srl Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili

Also Published As

Publication number Publication date
ATE273701T1 (de) 2004-09-15
EP0909171A1 (en) 1999-04-21
ITRM960479A0 (pt) 1996-07-05
ITRM960479A1 (it) 1998-01-05
WO1998001128A1 (en) 1998-01-15
DE69730330D1 (de) 2004-09-23
DE69730330T2 (de) 2005-02-10
IT1290801B1 (it) 1998-12-11
JP2000514437A (ja) 2000-10-31
PT909171E (pt) 2004-11-30
US6037373A (en) 2000-03-14
CA2260145A1 (en) 1998-01-15
KR100479669B1 (ko) 2005-06-13
CA2260145C (en) 2007-01-09
KR20000022515A (ko) 2000-04-25
US6166077A (en) 2000-12-26
ES2225968T3 (es) 2005-03-16

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